The human macrophage, an important component of the immune system, in large part functions to detect and damage foreign cells and to regulate certain immune interactions. The interaction between human macrophages and human erythrocyte target cells will serve as a study model for human macrophage-lymphoblastoid and myeloma cell interaction. Human erythrocytes coated with IgG or C3 will be bound to human macrophages, whereupon they become damaged (sphered) over time. The mechanism of the binding and sphering will be assessed by metabolic and pharmacologic (low concentrations of various lipid-soluble steroid analogues, levamisole) intervention, as well as by altering the macrophage membrane and the target erythrocyte (structurally, biochemically and immunologically). Comparisons will be made between isolated macrophage/monocyte subpopulations. Macrophage-lymphoblastoid cell and myeloma cell interactions will be examined as a model for macrophage-tumor cell interactions. The spontaneous interaction which we observe between these two former cells will be further defined. The effect of corticosteroids, levamisole, membrane cholesterol/phospholipid, immunologic activation and the requirement for specific macrophage subpopulations on these interactions and the consequences of such interactions will be studied. The regulation of normal and paraprotein immunoglobulin production in multiple myeloma will be studied with a focus on the role of the monocyte/macrophage in this interaction. In vitro results will be correlated with clinical findings. Using the myeloma idiotype as a prototype tumor-specific antigen the ability of anti-idiotype (tumor-specific) antibody to "arm" normal macrophages for specific tumor cell binding will also be assessed. A further understanding of the mechanisms involved in macrophage recognition and alteration of cell surfaces should provide insight leading to new approaches for harnessing the macrophages's ability to detect and alter tumor cells. These studies should also provide insight into the nature of activation and regulation of malignant (myeloma) cells and normal immunoglobulin-producing cells in a malignant lymphoproliferative disorder.